Afib patients with nonfatal brain bleeds at risk in months following event

Action Points

Note that this Danish population-based study demonstrated that the risk of ischemic stroke was high after intra-cerebral hemorrhage among patients with atrial fibrillation treated with warfarin.

Be aware that researchers were not able to completely confirm that it was the cessation of warfarin, per se, that led to the increased risk of ischemic stroke.

The risks of death and stroke were dramatically higher among atrial fibrillation patients who suffered nonfatal brain bleeds while on warfarin, compared with warfarin-treated patients who did not have bleeds in a registry-based cohort study from Denmark.

Patients who had intracranial hemorrhages (ICH) had a more than fivefold greater risk of death in the months following the event and a more than threefold increased risk for stroke, systemic embolism, or transient ischemic attack (TIA), researcher Gregory Lip, MD, of the University of Birmingham Center for Cardiovascular Sciences, Birmingham, England, and colleagues wrote in the journal CHEST.

Not surprisingly, the researchers also found that ICH events were followed by a decrease in warfarin usage.

'Reducing Bleeding Risk Has a Cost'

In an interview with MedPage Today, Lip said patients who experience a nonfatal ICH while on warfarin are often taken off the drug to reduce their risk for future bleeding events.

He said the study confirms that discontinuation of anticoagulants comes at a cost.

"Anecdotally, these patients have been perceived to be high risk, but the present study clearly shows that such patients are at very high risk of death and ischemic stroke," he said. "We have to balance ischemic stroke versus the potential for rebleeds in these patients."

Lip noted that patients with a history of ICH were excluded from clinical trials designed to compare the safety and efficacy of newer oral anticoagulant drugs with warfarin, even though they have a high risk for stroke and death.

While taking patients off oral anticoagulants for a time after an ICH seems prudent, Lip and colleagues wrote that there is much debate about when this treatment should resume.

"The lack of controlled clinical trials assessing whether to reverse oral anticoagulants and when to resume thromboprophylactic treatments poses a dilemma for clinicians: Having survived the acute phase, how does the increased risk for stroke/systemic embolism/TIA compare with the risk for recurrent ICH if oral anticoagulant therapy is not restarted?" they wrote.

To test their theory that ICH events are associated with an increased risk for thromboembolism and death, the researchers analyzed data from three Danish nationwide registries from 1999 to 2012 on Afib patients treated with warfarin.

They calculated event-rate ratios of stroke/thromboembolic events, major bleeding, and all-cause mortality stratified by ICH, and Cox proportional hazard models were used to compare event rates among ICH survivors.

Matched odds ratio was calculated for ICH occurrences within 0 to 3 months relative to the 3 to 6 months prior to a stroke/thromboembolic event, and the researchers also calculated the rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH.

Warfarin Prescription Rates Declined After ICH

A total of 58,815 Afib patients (median age, 72.6 years, 60% men) were included in the analysis, which revealed that:

Compared with patients who had not had brain bleeds, those who had them were at increased risk for stroke/systemic embolism/TIA (rate ratio, 3.67; 95% CI, 3.12-4.31) and death (rate ratio, 5.55; 95% CI, 5.20-5.92).

Patients with ICH events did not have an increased risk for major bleeding (rate ratio, 1.06; 95% CI, 0.81-1.39).

"Our study suggests that the risk for stroke/systemic embolism/TIA is, indeed, substantially increased, being up to a fivefold increase within the first 3 months after an ICH event," the researchers wrote.

Potential study limitations cited by Lip and colleagues included the observational design of the study, which might be subject to ascertainment bias and a lack of information on variables that might have further elucidated associations.

Lip noted that the new class of oral anticoagulants appear to be safer than warfarin for patients who have experienced ICH events, but he added that studies are needed to confirm this in this very high-risk population.

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